2DR Versus 3DR in a Prospective Randomized Controlled Switch Trial

NCT04553081 | Recruiting Phase 4 DMC

• 1 other identifier: BC-7052
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to monitor virological and immunological markers in participants who are switching from a classic triple drug regimen (3DR) to dual therapy (2DR). We aim to monitor whether this has an influence on different parameters such as severity of HIV disease (evaluated by viral load and viral reservoir size), presence of non-AIDS related health complications, impact the phenotype and function of the immune system. By conducting this study we want to assess whether switching from 3DR to 2DR implies an increased risk for 'subclinical' failure. We especially want to make sure that this switch does not increase the HIV reservoir, does not increase inflammation or immune exhaustion in patients living with HIV and that it can be considered as a safe long term alternative for the classic 3DR. The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in terms of the amount of intact replication competent HIV sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by an intact proviral DNA assay, present in blood CD4 cells.

Conditions

HIV-1-infection

Keywords

HIV; dual therapy; triple therapy; virological control; immune activation; metabolic complications

Outcome Measures

Primary Outcomes (1)

• Difference in amount of intact replication-competent HIV-1 sequences in CD4 cells between 2 regimens

  The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in HIV-1 infected individuals in terms of the amount of intact replication-competent HIV-1 sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by the intact proviral DNA assay (IPDA), present in blood CD4 cells.

  48 weeks

Secondary Outcomes (22)

• Full length sequencing of the virus

  240 weeks

• Quantification of interleukin-6 (IL-6)

  240 weeks

• Quantification of high-sensitivity C-reactive protein (hs-CRP)

  240 weeks

• Quantification of D-Dimers

  240 weeks

• Quantification of Human Leukocyte Antigen - DR isotype (HLA-DR)

  240 weeks

Study Arms (2)

Dovato

ACTIVE COMPARATOR

We aim to include 134 adult HIV-infected patients with HIV RNA \< 50 copies/mL for at least 3 months on any stable 2nd generation integrase based triple therapy antiretroviral regimen. Patients will be randomized 1:2 to switch to or stay on the triple regimen BIC/TAF/FTC (Biktarvy) (N=45) or to switch to the dual regimen DTG/3TC (Dovato) (N=89).

Drug: Dual versus triple therapy in treatment of HIV-1 infection.

Biktarvy

ACTIVE COMPARATOR

We aim to include 134 adult HIV-infected patients with HIV RNA \< 50 copies/mL for at least 3 months on any stable 2nd generation integrase based triple therapy antiretroviral regimen. Patients will be randomized 1:2 to switch to or stay on the triple regimen BIC/TAF/FTC (Biktarvy) (N=45) or to switch to the dual regimen DTG/3TC (Dovato) (N=89).

Drug: Dual versus triple therapy in treatment of HIV-1 infection.

Interventions

Dual versus triple therapy in treatment of HIV-1 infection. DRUG

cfr arm description

Also known as: not applicatble

Biktarvy; Dovato

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age = or \>18 years.
• Ability and willingness to provide written informed consent.
• Ability to attend the complete schedule of assessments and patient visits.
• Ability and willingness to have blood samples collected and stored indefinitely and used for various research purposes.
• HIV RNA \< 50 copies/mL for at least 3 months on a 2nd generation INSTI based regimen.
• Females of childbearing potential should be on effective contraception

You may not qualify if:

• Current presence of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification).
• Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (seroconversion= HBV antigen or viral load negative and positive HBV surface antibody).
• Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry.
• Pregnancy or breastfeeding.
• Patients unable to understand the study protocol or any other condition that in the investigator's opinion may compromise compliance with the study protocol
• Decompensated liver cirrhosis (Child-Pugh B/C)
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones)
• Psychiatric and psychological disorders, which in the opinion of the investigator, will interfere with the trial conduct or safety of the participant.
• Previous participation in a trial evaluating an immune modulating agent.
• Active drug or alcohol use/addiction such that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Treatment failure on an integrase inhibitor containing regimen and reported baseline resistance
• Creatinine Clearance \<50
• Tuberculosis treatment
• Documented M184V
• Previous virological failure \>200 copies/mL on NRTI

Sponsors & Collaborators

• University Hospital, Ghent: lead
• ViiV Healthcare: collaborator

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

Related Publications (2)

• Delporte M, Lambrechts L, Blomme EE, van Snippenberg W, Rutsaert S, Verschoore M, De Smet E, Noppe Y, De Langhe N, De Scheerder MA, Gerlo S, Vandekerckhove L, Trypsteen W. Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay. Clin Chem. 2025 Jan 3;71(1):203-214. doi: 10.1093/clinchem/hvae192.

  PMID: 39749517 DERIVED

• De Scheerder MA, Degroote S, Delporte M, Kiselinova M, Trypsteen W, Vincke L, De Smet E, Van Den Eeckhout B, Schrooyen L, Verschoore M, Muccini C, Vanherrewege S, Caluwe E, De Buyser S, Gerlo S, Blomme E, Vandekerckhove L. In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA). J Infect Dis. 2025 Feb 4;231(1):e91-e100. doi: 10.1093/infdis/jiae405.

  PMID: 39226296 DERIVED

Study Officials

• Linos Vandekerckhove

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Angelique De Scheerder

CONTACT

003293321349; marieangelique.descheerder@ugent.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: September 17, 2020
• Study Start: May 26, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)